Patent EP-0376524-A1 (EP)
Inventor: BUCKLE DEREK RICHARD
IPC: C07D493/04
Filed: 1989-12-08
Abstract: A compound of formula (I):
      or, where appropriate, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof 
wherein: 
one of A₁ or A₂ represents hydrogen and the other represents a group CF₃-Y- wherein Y represents -CF₂-, >C=O, or -CH(OH)-; 
Y₁ represents -O- -CH₂- or NR o  wherein R o  is hydrogen, alkyl or alkylcarbonyl;R₁ and R₂ independently represent hydrogen or alkyl; or R₁ and R₂ together represent a C₂₋₇ polymethylene moiety; 
R₃ represents hydrogen, hydroxy, alkoxy or acyloxy and 
R₄ is hydrogen or R₃ and R₄ together represent a bond; 
R₅ represents either a moiety of formula (a):  
      wherein A represents >C=X wherein X is O, S or NR₈ wherein R₈ represents CN, NO₂, COR₉ wherein R₉ is alkyl, amino, monoalkylamino, fluoroalkyl, phenyl or substituted phenyl or R₈ is SO₂R₉ wherein R₉ is as defined above, or A represents a bond; 
when A represents >C=X wherein X is O or S, then R₆ is hydrogen; alkyl optionally substituted by one or more groups or atoms selected from halogen, hydroxy, alkoxy, alkoxycarbonyl, carboxy or an ester or amide thereof, amino, monoalkylamino or dialkylamino; alkenyl; amino optionally substituted by an alkyl or alkenyl group or by an alkanoyl group optionally substituted by up to three halo atoms, by a phenyl group optionally substituted by alkyl, alkoxy or halogen; substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; and R₇ represents hydrogen or alkyl; 
or R₆ and R₇ together represent a linking chain of formula -A₃-A₄-, A₃ being attached to the nitrogen atom of the moiety -N-A- and A₄ being attached to the group A on the said moiety, and wherein A₃ represents a substituted or unsubstituted methylene group, A₄ represents 2 or 3 linking members, one of the linking members optionally representing O, S or NR and the other linking members each independently representing a substituted or unsubstituted methylene group; 
R represents hydrogen, alkyl, alkanoyl, phenyl C₁₋₄-­  alkyl, arylcarbonyl wherein the aryl group may be substituted or unsubstituted; or R is mono- or bi-cyclic- heteroarylcarbonyl; 
when A represents >C=X wherein X represents NR₈, then R₆ represents -NH.R₁₀ wherein R₁₀ is hydrogen, alkyl, C₃₋₆ cycloalkyl, alkenyl or alkynyl and R₇ is hydrogen or alkyl; or R₇ and R₁₀ together represent C₂₋₄ polymethylene; 
when A represents a bond, then R₆ and R₇ together with the nitrogen atom to which they are attached, form an unsaturated heterocyclic ring having 5 to 7 ring atoms, which ring atoms comprise up to 2 further nitrogen atoms and a carbon atom, the carbon atom being substituted with either an oxo group or a thioxo group, the remaining ring atoms being substituted or unsubstituted; 
or R₅ represents a moiety of formula (b):
      wherein T₁ represents >C-OH or N(O) n  wherein n is zero or 1 and T₂ together with C-T₁, when T₁ is >C-OH, represents an optionally substituted aryl group or T₂ together with CT₁, when T₁ is N(O) n , represents an optionally substituted, N- heteroaryl group; 
  or R₅ represents a moiety of formula (c):
      wherein L₁ represents O or NR₁₁ wherein R₁₁ represents hydrogen, alkyl, formyl, acetyl or hydroxymethyl, L₂ represents N or CL₄ wherein L₄ is hydrogen, halogen, formyl or hydroxymethyl, L₃ represents CH₂, O, S, >CHL₅ wherein L₅ is halogen or NL₆ wherein L₆ is hydrogen or alkyl and R₁₂ and R₁₃ each independently represent hydrogen or alkyl or R₁₂ together with R₁₃ represents oxo or thioxo; and p represents 1,2 or 3; a process for preparing such a compound, a pharmaceutical composition containing such a compound and the use of such a compcund and composition in medicine.